This review article summarizes (1) the varied effects of heme and heme oxygenase in tumorigenesis of different cancer types; (2) the molecular mechanisms of interaction of heme with regulatory and signaling proteins implicated in tumorigenesis, such as BACH1, PGRMC1, P53, CBS, sGC, and NOS; (3) the roles of altered heme levels and metabolism in the pathogenesis of diseases, including diabetes mellitus and Alzheimer’s dementia. This evidence concerns the gene TP53 and cancer.